Alterations in lipoprotein homeostasis during human experimental endotoxemia and clinical sepsis
B B A - Molecular and Cell Biology of Lipids , Volume 1771 - Issue 12 p. 1429- 1438
Cell wall constituents of bacteria are potent endotoxins initiating inflammatory responses which may cause dramatic changes in lipid metabolism during the acute phase response. In this study, the sequential changes in lipoprotein composition and lipid transfer and binding proteins during clinical sepsis and during low-dose experimental endotoxemia were followed. In addition, the effect on (phospho)lipid homeostasis by administration of reconstituted HDL (rHDL) prior to low-dose LPS administration was investigated. Changes in (apo)lipoprotein concentrations typical of the acute phase response were observed during clinical sepsis and experimental endotoxemia with and without the rHDL intervention. During clinical sepsis negative correlations between the acute phase marker C-reactive protein (CRP) and lecithin:cholesterol acyltransferase (LCAT) and cholesterylester transfer protein (CETP) activities were seen, whereas positive correlations between plasma phospholipid transfer protein (PLTP) activity and acute phase markers such as CRP and LPS binding protein were observed. Plasma lipid changes upon rHDL/LPS infusion were comparable with the control group (low-dose LPS only). PLTP activity decreased upon LPS infusion and transiently increased during rHDL infusion, whereas LCAT activity slightly decreased upon both LPS infusion and LPS/rHDL infusion. However, long-lasting increases of circulating HDL cholesterol, apo A-I and a high initial processing of both phosphatidylcholine (PC) and lyso-PC, were indicative for extensive rHDL and LDL remodelling. Both sepsis and experimental endotoxemia lead to a disbalance of lipid homeostasis. Depending on the magnitude of the inflammatory stimulus, LCAT and PLTP activities reacted in divergent ways. rHDL infusion did not prevent the lipid alterations seen during the acute phase response. However profound changes in both HDL and LDL phospholipid composition occurred upon rHDL infusion. This may be explained, at least in part, by the fact that PLTP as a positive acute phase protein, can accelerate the alterations in (phospho)lipid homeostasis thereby playing a role in the attenuation of the acute phase response.
|Endotoxemia, Inflammation, Lipoprotein, PLTP, Sepsis, rHDL|
|B B A - Molecular and Cell Biology of Lipids|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Levels, J.H.M, Pajkrt, D, Schultz, M.J, Hoek, F, van Tol, A, Meijers, J.C.M, & van Deventer, S. (2007). Alterations in lipoprotein homeostasis during human experimental endotoxemia and clinical sepsis. B B A - Molecular and Cell Biology of Lipids, 1771(12), 1429–1438. doi:10.1016/j.bbalip.2007.10.001